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Distribution of VIP mRNA and two distinct VIP binding sites in the developing rat brain: relation to ontogenic events
J M Hill1, D V Agoston, P Gressens
1Section on Developmental and Molecular Pharmacology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
The peptide neurotransmitter vasoactive intestinal peptide (VIP) has neurotrophic properties and influences neurobehavioral development. To assess the role of VIP during neural ontogeny, the present work traces the development of VIP mRNA with in situ hybridization and VIP receptors with in vitro autoradiography in rat central nervous system (CNS) from embryonic day 14 (E14) to the adult. VIP mRNA was not evident in the CNS until birth. Postnatally, it was expressed in several distinct brain regions, but its distribution bore little relation to that of VIP receptors. VIP receptors were present and expressed changing patterns of distribution throughout CNS development. The changing patterns were the result of 1) the transient appearance of GTP-insensitive VIP receptors in several regions undergoing mitosis or glial fasciculation and 2) the transient appearance of GTP-sensitive VIP receptors homogeneously distributed throughout the CNS during the first 2 postnatal weeks, the period of the brain growth spurt. At E14-16 VIP binding was dense throughout the brainstem and spinal cord, but limited in the rest of the brain. From E19 to postnatal day 14 (P14), while VIP binding was higher in germinal zones, it tended to be uniformly dense throughout the remainder of the brain. By P21 the adult pattern began to emerge; VIP binding was unevenly distributed and was related to specific cytoarchitectural sites. Since the expression of VIP in the CNS is limited to postnatal development but VIP receptors are abundant prenatally, we suggest that extraembryonic VIP may act upon prenatal VIP receptors to regulate ontogenic events in the brain.
Insights
Vasoactive intestinal peptide (VIP) receptors are present early in brain development, while VIP itself appears later. This suggests prenatal VIP may influence brain development through these early receptors.
Area of Science:
- Neuroscience
- Developmental Biology
- Neuroendocrinology
Background:
- Vasoactive intestinal peptide (VIP) is a peptide neurotransmitter with known neurotrophic effects.
- VIP influences neurobehavioral development, but its precise role during neural ontogeny is not fully understood.
Purpose of the Study:
- To investigate the developmental expression patterns of VIP mRNA and VIP receptors in the rat central nervous system (CNS).
- To elucidate the potential role of VIP and its receptors in regulating neural ontogeny.
Main Methods:
- In situ hybridization was used to trace the development of VIP mRNA.
- In vitro autoradiography was employed to map VIP receptor distribution.
- Studies were conducted in rat CNS from embryonic day 14 (E14) to adulthood.
Main Results:
- VIP mRNA expression was detected postnatally, not prenatally.
- VIP receptors were present throughout CNS development with dynamic distribution changes.
- Transient VIP receptor expression correlated with periods of cell division and brain growth.
Conclusions:
- Prenatal VIP receptor abundance suggests a role for extraembryonic VIP in regulating early brain development.
- The distinct temporal expression of VIP and its receptors indicates a complex regulatory mechanism during neural ontogeny.